Graduation Year

2004

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Psychology

Major Professor

Cheryl L. Kirstein, Ph.D

Committee Member

Mark Goldman, Ph.D.

Committee Member

Toru Shimizu, Ph.D.

Committee Member

James Willott, Ph.D.

Committee Member

Lynn Wecker, Ph.D.

Keywords

Addiction, Adolescence, Alcohol, Dopamine, Nucleus Accumbens

Abstract

The mesolimbic dopamine (DA) system has been implicated in providing the basis of pleasure, guiding the general mechanism of reinforcement as well as motivation. Support for these roles have grown from neurochemical research in the field of addiction. It is now well known that DA activity increases in the nucleus accumbens septi (NAcc) with exposure to addictive substances. Moreover, pharmacological manipulation of this system produces predictable changes in the administration of drugs of abuse, as well as natural reinforcers. This system is responsive to natural reinforcers and addiction may be the transference of routine mesolimbic function to environmental stimuli predictive of drug administration. The role of the NAcc in addiction specifically appears to be the facilitation of attention to drug-paired stimuli and addiction may be the behavioral manifestation of conditioned NAcc DA reactivity to the presence of drug-related stimuli. Although these findings have been reported in adults, few studies have focused on adolescence, the time when drug use/abuse begins. Adolescents may be particularly susceptible to addiction when considered in the light of this hypothesis. Recent research has revealed that the mesolimbic system of periadolescent animals is undergoing dramatic transition in functional tone. DA receptor and transporter levels are up regulated, synthesis rates are altered, and innervation from prefrontal cortex (PFC), involved in regulating tonic and phasic DA activity, is increasing. Consequently, during adolescence there is a dramatic change in tonic DA levels, variations in phasic responses to acute drug administration and alterations in how the system adapts to repeated drug exposure. The present study utilizes the procedures of conditioned place preference, Novelty preference and in vivo microdialysis to determine how this conditioning process changes during the period of adolescence. The results indicate that adolescents are different from adults not only on behavioral measures associated with drug abuse, but in their neurochemical responsiveness to alcohol, and that these differences are related to a general developmental aspect of adolescence that renders them susceptible to addiction.

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